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PDBsum entry 3ctr
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the rrm domain of poly(a)-Specific ribonuclease reveals a novel m(7)g-Cap-Binding mode.
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Authors
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T.Monecke,
S.Schell,
A.Dickmanns,
R.Ficner.
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Ref.
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J Mol Biol, 2008,
382,
827-834.
[DOI no: ]
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PubMed id
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Abstract
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Poly(A)-specific ribonuclease (PARN) is a processive 3'-exoribonuclease involved
in the decay of eukaryotic mRNAs. Interestingly, PARN interacts not only with
the 3' end of the mRNA but also with its 5' end as PARN contains an RRM domain
that specifically binds both the poly(A) tail and the 7-methylguanosine (m(7)G)
cap. The interaction of PARN with the 5' cap of mRNAs stimulates the
deadenylation activity and enhances the processivity of this reaction. We have
determined the crystal structure of the PARN-RRM domain with a bound m(7)G
triphosphate nucleotide, revealing a novel binding mode for the m(7)G cap. The
structure of the m(7)G binding pocket is located outside of the canonical
RNA-binding surface of the RRM domain and differs significantly from that of
other m(7)G-cap-binding proteins. The crystal structure also shows a remarkable
conformational flexibility of the RRM domain, leading to a perfect exchange of
two alpha-helices with an adjacent protein molecule in the crystal lattice.
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Figure 2.
Fig. 2. The crystallographic dimer mimics the NMR structure.
The protruding C-terminal α2 and α3 helices of each monomer
pack on the N-terminal β-sheet in a way that they mimic the NMR
structure (colored gray) of the PARN-RRM (PDB code: 1WHV). The
loop between the α2 and α3 helices corresponds to the fourth
β-strand of the canonical RRM fold.
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Figure 3.
Fig. 3. Detailed view of the cap binding site of the PARN-RRM
with bound m^7GTP. The m^7GTP cap (shown in ball-and-stick mode)
binds on the surface of the N-terminal part of the RRM domain
involving the loops connecting β2 and β3 strands as well as
the β1 strand and the α1 helix. The 2|F[o]| − |F[c]|
electron density (blue) corresponding to the bound m^7GTP is
contoured at 1.1 σ. The interacting residues are depicted in
ball-and-stick mode. The guanine moiety stacks on the side chain
of Trp475 and is bound by several hydrogen bonds. A water
molecule mediating hydrogen bonds between Thr458 and the
exocyclic oxygen O6 of the cap guanine is colored orange.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2008,
382,
827-834)
copyright 2008.
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